The indotricarbocyanine dye indocyanine green (ICG, cardiogreen) was first synthesized in the fifties (Heseltine D W (1959) U.S. Pat. No. 2,895,955) and was clinically approved as a diagnostic drug for the assessment of hepatic function and cardiac output, for which ICG exhibits favourable pharmacokinetic properties (Caesar J. et at. (1961) Clin. Sci. 21:43; Dorshow R. B. et al. (1998) J. Biomed. Optics 3:340). In the 1990s it has been discovered as diagnostic imaging agent and is frequently applied for fluorescence angiography to visualize vascular disorders in ophthalmology (Brancato R et al (1998) Semin. Ophthalmol. 13:189; Richard G., Soubrane G., Yanuzzi L. (1998) (eds) Fluorescein and ICG angiography, Thieme, Germany). ICG has been studied as potential NIR contrast agent for the detection of tumors both in animals (Reynolds J S et al. (1999) Photochem. Photobiol. 70:87; Licha K. et al. (2000) Photochem. Photobiol. 72:392) and patients (Ntziachristos V. et al. (2000) Proc. Nat. Acad. Sci. USA 97:2767). The rapid blood clearance of ICG providing only a short time window for contrast enhanced investigations and the rather poor fluorescence quantum efficiency in physiological environments has initiated attempts to design structurally related agents with improved properties (Landsman M. L. J. et al. (1976) J. Appl. Physiol. 40:575; Licha K. et al. (2000) Photochem. Photobiol. 72:392).
The use of fluorescent dyes for diagnostic imaging has been published in numerous patent applications and scientific papers. These publications have in common that they intend to provide improved diagnostic agents and/or agents utilizing structures such as ICG as part of novel chemical polymeric, particular, targeting and/or activatable entities (WO2005/019247, WO2004/028449, US2004/156785, WO2002/087498, WO2002/000265, US2002103517, WO 98/48846). ICG has also been described as a dye for the treatment of diseases using light irradiation (U.S. Pat. No. 6,443,976; Tuchin V. V. et al. (2003) Lasers Surg. Med. 33:296; Greenwell T. J. et al. (2001) Eur. J. Surg. Oncol. 27:368).
US2004156785 describes bioactivatable contrast agents (MRI and optical) comprising ICG and their use in imaging.
The diagnostic imaging of rheumatoid arthritis using light is a known experimental approach (Scheel A. K. et al. (2002) Arthrit. Rheum. 46:1177). The application of fluorescent dyes as imaging probes has been described in the literature using different types of agents (Chen W T et al. (2005) Arthritis Res. Ther. 7:R310; Hansch A. et al. (2004) Invest Radiol 39:626; Wunder A. et al. (2004) Arthritis Rheum. 50:2459). However, none of these publications described the particular suitability of indocarbocyanine dyes, in particular of ICG as diagnostic imaging agent for imaging of inflammatory diseases, in particular of rheumatoid arthritis.